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Gene Review

Tfrc  -  transferrin receptor

Rattus norvegicus

Synonyms: TR, TfR, TfR1, Transferrin receptor protein 1, Trfr
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Disease relevance of Tfrc


Psychiatry related information on Tfrc

  • Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease [6].
  • The expression of many TH target genes is regulated by TH only for a limited critical period, although TH receptor (TR) expression is not greatly altered after such period [7].

High impact information on Tfrc

  • Recently, the c-erb A proto-oncogene products have been shown to be nuclear thyroid hormone (T3) receptors (TR) by sequence similarity with other steroid receptors and by their ability to bind thyroid hormone [8].
  • When conjugated to an antibody to the transferrin receptor, however, NGF crossed the blood-brain barrier after peripheral injection [9].
  • Vesicles containing a dendritic protein, transferrin receptor (TfR), were preferentially transported into dendrites and excluded from axons [10].
  • Since there are two major thyroid hormone receptor (TR) isoforms, TR alpha and TR beta, it is not known how the mutant receptor mediates a dominant negative effect [11].
  • The synaptophysin-containing vesicles were labeled if a surface-labeled cell was warmed to 37 degrees C, comigrated with transferrin receptor-containing vesicles on velocity and density gradients, and could be completely immunoadsorbed by anti-LDL receptor tail antibodies [12].

Chemical compound and disease context of Tfrc


Biological context of Tfrc

  • The molecular mechanisms controlling TfR gene expression in vivo during I/R of rat liver were investigated by molecular biology procedures [1].
  • RNA bandshift analysis showed that iron regulatory protein (IRP) activity was decreased in the first hours of reperfusion, thus indicating that IRP-mediated mRNA stabilization was not involved in early TfR upregulation [1].
  • In conclusion, HIF-1 mediated activation of TfR gene transcription and IRP-mediated increase of TfR mRNA stability ensure a steady induction of TfR, and hence higher iron uptake in reperfused rat liver [1].
  • Transferrin receptor was found to be synthesized early in AEC cultures with the alveolar type II cell-like phenotype [18].
  • These findings suggested that Tf-Fe transport across the membrane of astrocytes is mediated by Tf-TfR endocytosis [19].

Anatomical context of Tfrc


Associations of Tfrc with chemical compounds


Physical interactions of Tfrc


Enzymatic interactions of Tfrc

  • In preliminary studies, monensin (10 microM) produced a 32%-50% shift of Tf-R from the surface to the inside, whereas short-term incubation with epidermal growth factor (0.17 mM) brought about no clear-cut Tf-R redistribution [25].

Co-localisations of Tfrc


Regulatory relationships of Tfrc


Other interactions of Tfrc


Analytical, diagnostic and therapeutic context of Tfrc


  1. Transferrin receptor gene expression and transferrin-bound iron uptake are increased during postischemic rat liver reperfusion. Tacchini, L., Fusar Poli, D., Bernelli-Zazzera, A., Cairo, G. Hepatology (2002) [Pubmed]
  2. Iron, ferritin, transferrin, and transferrin receptor in the adult rat retina. Yefimova, M.G., Jeanny, J.C., Guillonneau, X., Keller, N., Nguyen-Legros, J., Sergeant, C., Guillou, F., Courtois, Y. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  3. Transferrin receptors and selective iron deposition in pancreatic B cells of iron-overloaded rats. Lu, J.P., Hayashi, K., Okada, S., Awai, M. Acta Pathol. Jpn. (1991) [Pubmed]
  4. Transferrin and transferrin receptor gene expression and iron uptake in hepatocellular carcinoma in the rat. Pascale, R.M., De Miglio, M.R., Muroni, M.R., Simile, M.M., Daino, L., Seddaiu, M.A., Pusceddu, S., Gaspa, L., Calvisi, D., Manenti, G., Feo, F. Hepatology (1998) [Pubmed]
  5. Iron accumulation, iron-mediated toxicity and altered levels of ferritin and transferrin receptor in cultured astrocytes during incubation with ferric ammonium citrate. Hoepken, H.H., Korten, T., Robinson, S.R., Dringen, R. J. Neurochem. (2004) [Pubmed]
  6. Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease. Kordower, J.H., Charles, V., Bayer, R., Bartus, R.T., Putney, S., Walus, L.R., Friden, P.M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  7. Postnatal changes of steroid receptor coactivator-1 immunoreactivity in rat cerebellar cortex. Yousefi, B., Jingu, H., Ohta, M., Umezu, M., Koibuchi, N. Thyroid (2005) [Pubmed]
  8. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Izumo, S., Mahdavi, V. Nature (1988) [Pubmed]
  9. Blood-brain barrier penetration and in vivo activity of an NGF conjugate. Friden, P.M., Walus, L.R., Watson, P., Doctrow, S.R., Kozarich, J.W., Bäckman, C., Bergman, H., Hoffer, B., Bloom, F., Granholm, A.C. Science (1993) [Pubmed]
  10. The role of selective transport in neuronal protein sorting. Burack, M.A., Silverman, M.A., Banker, G. Neuron (2000) [Pubmed]
  11. New insights on the mechanism(s) of the dominant negative effect of mutant thyroid hormone receptor in generalized resistance to thyroid hormone. Yen, P.M., Sugawara, A., Refetoff, S., Chin, W.W. J. Clin. Invest. (1992) [Pubmed]
  12. Synaptophysin is sorted from endocytotic markers in neuroendocrine PC12 cells but not transfected fibroblasts. Linstedt, A.D., Kelly, R.B. Neuron (1991) [Pubmed]
  13. Induction of transferrin receptor by ethanol in rat primary hepatocyte culture. Suzuki, M., Fujimoto, Y., Suzuki, Y., Hosoki, Y., Saito, H., Nakayama, K., Ohtake, T., Kohgo, Y. Alcohol. Clin. Exp. Res. (2004) [Pubmed]
  14. Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine. Legssyer, R., Josse, C., Piette, J., Ward, R.J., Crichton, R.R. J. Inorg. Biochem. (2003) [Pubmed]
  15. Increased divalent metal transporter 1 expression might be associated with the neurotoxicity of L-DOPA. Chang, Y.Z., Ke, Y., Du, J.R., Halpern, G.M., Ho, K.P., Zhu, L., Gu, X.S., Xu, Y.J., Wang, Q., Li, L.Z., Wang, C.Y., Qian, Z.M. Mol. Pharmacol. (2006) [Pubmed]
  16. Alteration at translational but not transcriptional level of transferrin receptor expression following manganese exposure at the blood-CSF barrier in vitro. Li, G.J., Zhao, Q., Zheng, W. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
  17. Effects of gestational hypoxia on mRNA levels of Glut3 and Glut4 transporters, hypoxia inducible factor-1 and thyroid hormone receptors in developing rat brain. Royer, C., Lachuer, J., Crouzoulon, G., Roux, J., Peyronnet, J., Mamet, J., Pequignot, J., Dalmaz, Y. Brain Res. (2000) [Pubmed]
  18. Phenotype-dependent synthesis of transferrin receptor in rat alveolar epithelial cell monolayers. Widera, A., Beloussow, K., Kim, K.J., Crandall, E.D., Shen, W.C. Cell Tissue Res. (2003) [Pubmed]
  19. Transferrin-bound and transferrin free iron uptake by cultured rat astrocytes. Qian, Z.M., Liao, Q.K., To, Y., Ke, Y., Tsoi, Y.K., Wang, G.F., Ho, K.P. Cell. Mol. Biol. (Noisy-le-grand) (2000) [Pubmed]
  20. Characterization of rat transferrin receptor cDNA: the regulation of transferrin receptor mRNA in testes and in Sertoli cells in culture. Roberts, K.P., Griswold, M.D. Mol. Endocrinol. (1990) [Pubmed]
  21. A morphological study of the developmentally regulated transport of iron into the brain. Moos, T., Morgan, E.H. Dev. Neurosci. (2002) [Pubmed]
  22. Increase in surface expression of transferrin receptors on cultured hepatocytes of adult rats in response to iron deficiency. Muller-Eberhard, U., Liem, H.H., Grasso, J.A., Giffhorn-Katz, S., DeFalco, M.G., Katz, N.R. J. Biol. Chem. (1988) [Pubmed]
  23. Comparison of iron-59, indium-111, and gallium-69 transferrin as a macromolecular tracer of vascular permeability and the transferrin receptor. Otsuki, H., Brunetti, A., Owens, E.S., Finn, R.D., Blasberg, R.G. J. Nucl. Med. (1989) [Pubmed]
  24. Transferrin receptors in rat plasma. Beguin, Y., Huebers, H.A., Josephson, B., Finch, C.A. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  25. Quantification of rat hepatocyte transferrin receptors with poly- and monoclonal antibodies and protein A. Rudolph, J.R., Regoeczi, E., Southward, S. Histochemistry (1988) [Pubmed]
  26. Endogenous presenilin-1 targets to endocytic rather than biosynthetic compartments. Lah, J.J., Levey, A.I. Mol. Cell. Neurosci. (2000) [Pubmed]
  27. Aluminium toxicity and iron homeostasis. Ward, R.J., Zhang, Y., Crichton, R.R. J. Inorg. Biochem. (2001) [Pubmed]
  28. Temporal responses in the disruption of iron regulation by manganese. Kwik-Uribe, C., Smith, D.R. J. Neurosci. Res. (2006) [Pubmed]
  29. Colocalization of synaptophysin with transferrin receptors: implications for synaptic vesicle biogenesis. Cameron, P.L., Südhof, T.C., Jahn, R., De Camilli, P. J. Cell Biol. (1991) [Pubmed]
  30. Selenium and vitamin E deficiency impair transferrin receptor internalization but not IL-2, IL-2 receptor, or transferrin receptor expression. Pighetti, G.M., Eskew, M.L., Reddy, C.C., Sordillo, L.M. J. Leukoc. Biol. (1998) [Pubmed]
  31. Calmodulin dependence of transferrin receptor recycling in rat reticulocytes. Grasso, J.A., Bruno, M., Yates, A.A., Wei, L.T., Epstein, P.M. Biochem. J. (1990) [Pubmed]
  32. Thrombin preconditioning attenuates brain edema induced by erythrocytes and iron. Hua, Y., Keep, R.F., Hoff, J.T., Xi, G. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  33. Impaired retinal iron homeostasis associated with defective phagocytosis in Royal College of Surgeons rats. Yefimova, M.G., Jeanny, J.C., Keller, N., Sergeant, C., Guillonneau, X., Beaumont, C., Courtois, Y. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  34. Transferrin receptor expression of the hyperplastic lesions of hepatocyte in experimental hepatocarcinogenesis. Park, C.I., Park, Y.N., Jung, W.H. J. Korean Med. Sci. (1995) [Pubmed]
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